AJNR: neuroimaging of retinal angiopathy with leukoencephalopathy and multisystem damage

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is an inherited disorder
caused primarily by mutations in the TREX1 gene.
The histologic feature of RVCL-S is systemic vascular lesions
of medium- and small-caliber arteries and veins.
Clinically, it usually develops after the age of 35 to 40 years and is characterized by
vascular retinopathy, Raynaud's phenomenon, migraine, and multi-organ dysfunction (including nephropathy, liver disease, anaemia, and subclinical hypothyroidism).

To date, few studies have described neuroimaging findings, and these reports have focused on symptomatic patients with advanced RVCL-S
.
Previous studies have described 3 lesion types:

1) focal-to-fusion non-enhanced white matter lesions (WML),

2) WML with dotted strengthening,

3) Ring-enhanced lesions with peripheral T2 hyperintensity (edema/gliosis) and/or diffusion inhibition
.
These lesions with peripheral edema become larger and have a mass effect, called pseudotumors
.
RVCL-S remains an easily missed disease, in part due to a lack of awareness
among radiologists.

To date, there have been no reports of high-quality systematic follow-up neuroimaging for pre-symptomatic and symptomatic mutation carriers
.

Figure 1.
MR imaging features
of a typical RVCL-S lesion in a 60-year-old man.
Periventricular and deep WML
are visible in sagittal (A) and axial FLAIR (B).
3D-T1-weighted Gd images (C) show ring-enhancing lesions next to the right occipital angle and punctate intensified lesions (white arrows)
in the left occipital angle.
Punctate SWI artifacts (D)
are visible in the center of these lesions.
DWI high signal (E) and ADC low signal (F) can be seen in the lesion, which is diffusion inhibition:

Figure 2.
60-year-old woman with punctate lesions
of the basal ganglia and cerebellum.
A.
The putamen and caudate head point-like intensified lesions on the right (white arrows).

B.
Bilateral cerebellar punctate strengthening lesions (white arrows):

Fig.
3.
In a 55-year-old woman, the lesions showed long-term intensification and diffusion inhibition
during the follow-up period of 31 months.
3D-T1-weighted Gd imaging and DWI(A) at baseline showed point-enhanced lesions on the right with diffusion inhibition (white arrows), and after 31 months (B) showed lesion migration (migrates) to the right ventricle (white arrows).

At this point, the lesion is linear-intensive with partial annular enhancement and diffusion suppression (ADC low signal, picture not provided):

Figure 4.
Imaging features
of a 45-year-old female pseudotumor.
A 30 mm diameter annular enhancement lesion located on the lateral left frontal horn, with multiple punctate magnetic sensitivity artifacts and diffusion inhibition in the center of the lesion, and peripheral extensive vasogenic edema with mass effect (a, FLAIR.
B，3DT1Gd.
C，SWI.
D，DWI）：

In September 2021, Mark C.
Kruit et al.
from the Netherlands reported magnetic resonance imaging results in 29 TREX1 mutation carriers (20-65 years old) and 17 mutation carriers (30-65 years old
) in AJNR.
Mutation carriers under the age of 40 show a significant number of punctate white matter lesions, but scans are usually subtle.

From the age of 40 years, supratentorial lesions evolve into long-term intensification (median, 24 months) and diffusion inhibition (median, 8 months).

Among these lesions, central magnetic artifacts (central susceptibility artifacts) appeared, at least partially corresponding to calcifications
on existing CTs.
Some lesions (n=2) also show peripheral edema and mass effect (pseudotumor).

Cerebellar punctate lesions occur mainly in individuals
over 50 years of age.
These typical neuroimaging findings should help neuroradiology identify RVCL-S
.